IgA nephropathy is one of the various diagnoses of glomerulonephritis, and is known to be the most frequent glomerulonephritis in foreign countries as well as Korea. Its cause is not well known. When bacteria invade a body, an immunity substance referred to as an “antibody” is required to struggle against the bacteria. However, a phenomenon in which immunoglobulin A (IgA), one of such antibodies, reaches a kidney's glomerulus and destroys it without struggling against bacteria is referred to as IgA nephropathy. At present, the representative biomarkers for determining the degree of progression of IgA nephropathy include proteinuria and creatine. However, proteinuria is highly related to a marker for other diseases in that it is also a marker indicating occurrence of hypertension and cardiovascular diseases as well as IgA nephropathy, and thus it is difficult to directly determine the degree of progression of diabetic nephropathy. Also, TGBM nephropathy causes symptoms such as haematuria and proteinuria. Although such symptoms are similar to those of IgA nephropathy, TGBM nephropathy is a disease with a relatively favorable prognosis. However, it is impossible to accurately diagnose IgA nephropathy by only such a history (including a cause, symptoms, and progress with the passage of time, etc. of a patient's disease), and a kidney biopsy is required for accurate diagnosis.
Accordingly, when a novel diagnosis marker having clinically high specificity and sensitivity, and a monoclonal antibody for detecting the marker are developed, it is possible to develop a kit which can diagnose diabetic nephropathy early and the degree of progression can be predicted in advance.
Accordingly, the present inventors attempted to conduct research for overcoming problems of the above described conventional technologies. As a result, they have completed the present invention by identifying biomarkers of diseases such as IgA nephropathy and TGBM nephropathy through a target proteomics technique.
IgA nephropathy is the most frequent glomerulonephritis in Korea. It may occur in all age groups, but mainly occurs in people in their teens and twenties. Its clinical features are various. Intermittent visible haematuria may occur accompanied by upper respiratory tract infection, or persistent microscopic haematuria and proteinuria occur. In some cases, IgA nephropathy is expressed as nephritic syndrome, acute nephritis, or hypertension. Also, in many cases, IgA nephropathy progresses while being unknown to patients, and then is found as chronic renal failure. It has been reported that IgA nephropathy is slowly progresses, and finally progresses to a terminal kidney disease in about 30% or more of patients within 20 years. However, IgA nephropathy shows various clinical progresses. Known risk factors that have an effect on prognosis include persistent proteinuria, depression in renal function, persistent hypertension, old age, being male, and histological findings, etc. IgA nephropathy is a kind of immune complex-mediated glomerular disease. Its basic cause is a control disorder of an immune reaction against an antigen coming into a mucous membrane, etc., by which polymeric IgA1 is excessively produced in bone marrow, and at the same time the structure deficiency of IgA1 occurs. As a result, polymeric IgA1 is deposited in mesangium, and damage is caused by mediators. Optical microscopic findings on IgA nephropathy characteristically include focal or diffuse cell proliferation, and expansion of extracellular matrix in mesangium. The cell proliferation occurs in various ways and even causes crescent formation. Vascular lesion and tubulointerstitial lesion are also observed. Immunofluorescence is necessary for a diagnosis of IgA nephropathy because it shows that IgA is significantly deposited in mesangium. In general, IgA is deposited together with C3, IgG, IgM, etc. Electron microscopic findings are characterized in that high electron dense deposits are observed in mesangium or its periphery, and subendothelial deposits are locally observed in the periphery of the mesangium.
There are patent disclosures concerning research on a diagnosis method of IgA nephropathy. Korean laid-open patent No. 1999-82292 discloses a method of obtaining a novel gene from an IgA renopathy patient's leukocytes by using a differential•display method, an IgA nephropathy diagnostic agent including oligonucleotide derived from a leukocyte, and a therapeutic agent. Korean registered patent No. 528664 discloses an IgA protein for diagnosing diabetic retinopathy, a diagnostic kit including an IgA protein antibody, and a diagnosis method. Korean laid-open patent No. 2004-54609 discloses a method for relating a gene expression profile to a protein expression profile in identifying a target protein related to a disease such as an autoimmune disease to identify new drug development and a diagnosis marker. US patent publication No. 2007/87448 discloses a general method for diagnosing the progress stage of a disease by collecting a physiological specimen from blood and urine of a subject, obtaining a spectroscopic peak through the mass spectrometry of the specimen, and using protein profile analysis information obtained from the peak. Korean registered patent No. 792630 discloses a method for early diagnosis and progress stage determination of diabetic nephropathy in diabetes mellitus, in which the occurrence, early diagnosis, progress stage, and symptom severity of diabetic nephropathy in diabetes mellitus are determined from blood of a person, and a monoclonal antibody prepared based on an identified protein is used for an immunoassay kit.
Although it is important to diagnose early and treat IgA nephropathy or TGBM nephropathy before serious depression in renal function occurs in IgA nephropathy patients or TGBM nephropathy patients, it is difficult to determine whether to carry out an invasive test such as renal biopsy in young adults showing only hematuria or proteinuria without symptoms in order to diagnose the nephropathy. Furthermore, in a case of renal biopsy, it is difficult to actually carry out the biopsy in all patients for various reasons. Therefore, there is a need to develop a novel method or kit for diagnosing IgA nephropathy or TGBM nephropathy, which is simple and accurate.